We have extended our mechanistic studies of virus-receptor interactions, with focus on two specific enveloped viruses: 1) Hepatitis C virus (HCV). Using specialized mammalian producer cell line carrying a West Nile virus replicon, we have devised a novel system to generate infectious HCV particles (genotype 1a) in which all viral-encoded components (proteins and RNA) are derived from HCV. We have shown that the system can generate infectious particles carrying full-length HCV genomes that replicate in HCV-permissive target cells as well as human liver slices. Evidence suggests that the ability of the WNV-replicon cell line to secrete infectious HCV particles is due not to ongoing function of the WNV replicon, but rather to intracellular changes (presumably including membrane rearrangements) induced by the replicon (Triyatni et al., submitted manuscript under revision). 2) Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8). As we have previously reported for KSHV glycoprotein gH, we are seeking to make soluble truncated constructs for gB and K8.1A. These efforts have proven difficult, probably due to binding of the secreted proteins to surface glycoproteins on the producer cells. To resolve this, we have begun studies using CHO mutant cells defective in proteoglycan synthesis.